RU2451681C2 - Method of producing amide compound - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing an amide compound of formula

(3). The disclosed method involves reaction of an aniline compound of formula

(1) and an aldehyde compound of formula

(2) in a solvent in the presence of an oxidant such as oxygen, peroxide, chromic acid or salt thereof. In the given formulae, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ assume values given in the claim. In particular, R¹, R² and R³ independently denote a C_1-C₆ alkyl group which can be substituted with a halogen atom or similar; R⁴, R⁵, R⁶ and R⁷ independently denote a halogen atom or similar.

EFFECT: disclosed method enables to obtain compounds of formula (3), which have excellent regulating activity on harmful arthropods.

3 cl, 5 tbl, 18 ex

Description

FIELD OF THE INVENTION

The present invention relates to a method for producing an amide compound.

State of the art

Some amide compounds are described in WO 01/70671 and WO 03/015518.

Description of the invention

Problems to be Solved by the Invention

The present invention provides a method for producing an amide compound represented by the following formula (3) and having excellent regulatory activity against harmful arthropods.

Ways to solve problems

The present invention provides a method for producing an amide compound represented by the formula (3)

(hereinafter referred to as compound (3)):

[Chemical formula 3]

where R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ^{7 are} defined below, including the interaction of aniline compounds represented by formula (1) (hereinafter referred to as compound (1)):

[Chemical formula 1]

where R ¹ represents a C1-C6 alkyl group optionally substituted by at least one halogen atom, R ² represents a hydrogen atom or a C1-C6 alkyl group optionally substituted by at least one halogen atom, R ³ represents C1-C6 alkyl group optionally substituted by at least one halogen atom, C3-C6 alkoxyalkyl group optionally substituted by at least one halogen atom, C3-C6 alkenyl group optionally substituted by at least one halogen atom or C3-C 6 an alkynyl group optionally substituted by at least one halogen atom, R ⁴ represents a halogen atom or a C1-C6 alkyl group optionally substituted by at least one halogen atom, and R ⁵ represents a hydrogen atom, a halogen atom, a cyano group or a C1-C6 alkyl group optionally substituted with at least one halogen atom with an aldehyde compound represented by the formula (2) (hereinafter referred to as compound (2)):

[Chemical formula 2]

where R ⁶ represents a hydrogen atom, a halogen atom, a cyano group, a C1-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted by at least one halogen atom, a C1-C6 alkylsulfinyl group, optionally substituted by at least one halogen atom, or a C1-C6 alkylsulfonyl group optionally substituted by at least one halogen atom, and R ⁷ imagine represents a halogen atom or a C1-C6 alkyl group optionally substituted by at least one halogen atom in a solvent in the presence of an oxidizing agent selected from the following group A: (a) oxygen, (b) peroxide and (c) chromic acid or salt.

The implementation of the invention

In accordance with the method of the present invention, it is possible to obtain a compound (3) having excellent regulatory activity against harmful arthropods.

BEST MODE FOR CARRYING OUT THE INVENTION

In the method of the present invention, from 0.5 to 2 mol of the compound (2) is usually used per 1 mol of compound (1). The amounts of compound (1) and compound (2) used can be changed depending on the reaction situation.

The interaction of compound (1) with compound (2) is carried out in the presence of an oxidizing agent selected from group A. Specific examples of the oxidizing agent included in group A are the following oxidizing agents.

(a) Oxygen

The oxygen used in the method of the present invention may be oxygen gas per se, a mixture of gases obtained by diluting oxygen gas with another gas, such as nitrogen gas or carbon dioxide gas or air. When using gaseous oxygen or air as an oxidizing agent, the reaction is carried out by mixing a solution of compound (1) and compound (2) in a solvent in an atmosphere of gaseous oxygen or air, sparging gaseous oxygen or air into this solution. The reaction can be carried out at normal pressure or at elevated pressure.

The amount of oxygen used in the reaction is preferably from 1 to 2 mol per 1 mol of compound (2) and may vary depending on the reaction situation.

(b) Peroxide (peracid)

Peroxide is an inorganic or organic compound containing an —O — O— bond in a molecule. Examples of the peroxide used in the method of the present invention include inorganic peroxide, such as sodium persulfate, potassium persulfate, ammonium persulfate and hydrogen peroxide; an alcohol peroxide such as tert-butyl hydroperoxide; a carboxylic anhydride peroxide such as benzoyl peroxide; carboxylic acid peroxide such as peracetic acid, trifluoronacetic acid and methachloroperbenzoic acid (mCPBA); and organic peroxide, such as ditrimethylsilyl peroxide.

The amount of peroxide used in the reaction is preferably from 1 to 2 mol per 1 mol of compound (2) and may vary depending on the reaction situation.

(c) Chromic acid or its salt

Examples of chromic acid or a salt thereof used in the method of the present invention include VI-valent chromium compounds such as chromic anhydride, chromic acid, sodium chromate, potassium chromate, sodium dichromate, potassium dichromate, pyridinium chlorochromate, pyridinium dichromate and chromyl chloride.

The amount of chromic acid or its salt used in the reaction is preferably from 1 to 2 equivalents per 1 mol of compound (2) and may vary depending on the reaction situation.

The reaction described above in the method of the present invention is carried out in a solvent. Examples of solvents that can be used in this reaction include ethereal solvents such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogenated hydrocarbon solvents such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbon solvents such as hexane, heptane, toluene, benzene and xylene; nitrile solvents such as acetonitrile; amide solvents such as N, N-dimethylformamide; solvents based on nitrogen-containing cyclic compounds, such as N-methylpyrrolidone and 1,3-dimethyl-2-imidazolidinone; aprotic solvents, for example sulfoxide solvents such as dimethyl sulfoxide; carboxylic acid solvents such as acetic acid; ketone solvents such as acetone and isobutyl methyl ketone; ester solvents such as ethyl acetate; alcohol solvents such as 2-propanol and tert-butyl alcohol; and water. You can use a mixture of two or more solvents, and the reaction can be carried out in a single-phase system or in a two-phase system.

The reaction temperature is usually in the range from 0 to 150 ° C. The duration of the reaction is usually in the range from instant to 72 hours.

If necessary, an acid may be present in this reaction. Examples of an acid that can be used include mineral acids, such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and perchloric acid; carboxylic acids such as acetic acid and benzoic acid; sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; boron compounds such as boron trifluoride; aluminum compounds such as aluminum (III) chloride and aluminum (III) isopropoxide; titanium compounds such as titanium (IV) tetrachloride and titanium (IV) isopropoxide; zinc compounds such as zinc (II) chloride; iron compounds such as iron (III) chloride and the like.

When an acid is used in the reaction, the amount of this acid used is usually from 0.001 to 1 mol per 1 mol of compound (2), and the amount used can vary depending on the reaction situation.

After completion of the reaction, compound (3) can be isolated by pouring the reaction mixture into water, followed by extraction with an organic solvent, or pouring the reaction mixture into water, followed by separation of the precipitate formed by filtration. The isolated compound (3) can be further purified by recrystallization, chromatography or the like.

Next, methods for preparing compound (1) and compound (2) used in the method of the present invention will be explained.

Compound (1) can be obtained according to the following scheme (1).

Scheme (1):

[Chemical formula 4]

where R ¹ , R ² , R ³ , R ⁴ and R ^{5 are as} defined above.

Compound (4) → compound (1)

Compound (7) is usually used in an amount of 1 mol per 1 mol of compound (4).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; alcohols such as methanol, ethanol and isopropyl alcohol; and mixtures thereof.

Among the compounds (1), the compound represented by the formula (1-i) can be obtained according to the following scheme (2).

Scheme (2):

[Chemical formula 5]

where R ¹² represents a C1-C6 alkyl group optionally substituted by at least one halogen atom, L ¹ represents a leaving group (e.g., a halogen atom, methanesulfonyloxy group or p-toluenesulfonyloxy group), and R ³ , R ⁴ and R ⁵ defined above.

Compound (4) → compound (5-i)

Compound (7-i) is usually used in an amount of 1 mol per 1 mol of compound (4).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; alcohols such as methanol, ethanol and isopropyl alcohol; and mixtures thereof.

Compound (5-i) → compound (1-i)

1. If necessary, the amino group (-NH ₂ ) in the benzene ring of compound (5-i) can be protected with a suitable protecting group (eg, N-benzylidene group, N- (1-methyl) ethylidene group) described in Green's book Protective Groups in Organic Synthesis (WILEY) and so on.

2. Compound (9-i) or compound (10-i) is usually used in an amount of 2 mol per 1 mol of compound (5-i) or its derivative in which the amino group is protected. Examples of the base used in this reaction include metal carbonates such as potassium carbonate and sodium carbonate; metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; and metal hydrides such as sodium hydride.

3. The compound (1-i) in which the amino group is protected can be deprotected under known conditions.

Among the compounds (1), the compound represented by the formula (1-ii) can be obtained according to the following scheme (3).

Scheme (3):

[Chemical formula 6]

where R ¹ , R ³ , R ⁴ and R ^{5 are as} defined above.

Compound (4) → compound (6-ii)

Compound (8-ii) is usually used in an amount of 1 mol per 1 mol of compound (4).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; alcohols such as methanol, ethanol and isopropyl alcohol; and mixtures thereof.

Compound (6-ii) → compound (1-ii)

1. If necessary, the amino group (-NH ₂ ) in the benzene ring of compound (6-ii) can be protected with a suitable protecting group (eg, N-benzylidene group, N- (1-methyl) ethylidene group) described in Green's book Protective Groups in Organic Synthesis (WILEY) and so on.

2. Compound (11) is usually used in an amount of 1 mol per 1 mol of compound (6-ii) or a derivative thereof in which the amino group is protected. Examples of the base used in this reaction include metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate; metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; and metal hydrides such as sodium hydride.

3. The compound (1-ii) in which the amino group is protected can be deprotected under known conditions.

Among the compounds (1), the compound represented by the formula (1-iii) can be obtained according to the following scheme (4).

Scheme (4):

[Chemical formula 7]

where R ¹⁰ and R ²⁰ represent a C1-C6 alkyl group optionally substituted with at least one halogen atom, and R ³ , R ⁴ and R ⁵ and L ^{1 are as} defined above.

Compound (4) → compound (5-ii)

Compound (7-iv) is usually used in an amount of 1 mol per 1 mol of compound (4).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; alcohols such as methanol, ethanol and isopropyl alcohol ;, and mixtures thereof.

Compound (5-ii) → compound (1-iii)

1. If necessary, the amino group (-NH ₂ ) in the benzene ring of compound (5-ii) can be protected with a suitable protecting group (eg, N-benzylidene group, N- (1-methyl) ethylidene group) described in Green's book Protective Groups in Organic Synthesis (WILEY) and so on.

2. Compound (9-iii) or compound (10-iii) is usually used in an amount of 1 mol per 1 mol of compound (5-ii) or its derivative in which the amino group is protected. Examples of the base used in this reaction include metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate; metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; and metal hydrides such as sodium hydride.

3. The compound (1-iii) in which the amino group is protected can be deprotected under known conditions.

Compound (4) is a known compound or can be obtained according to the following scheme (5).

Scheme (5):

[Chemical formula 8]

where R ⁴ and R ^{5 are as} defined above.

Compounds (7-i), (7-ii), (7-iii) and (7-iv) are known compounds or can be obtained according to the following scheme (6).

Scheme (6):

[Chemical formula 9]

where R ^a represents a C1-C6 alkyl group optionally substituted with at least one halogen atom, and R ³ and R ^{12 are} defined above.

Among the compounds (7), the compound represented by the formula (7-v) can be obtained according to the following scheme (7).

Scheme (7):

[Chemical formula 10]

where R ^b represents a C1-C6 alkyl group optionally substituted by at least one halogen atom, and R ^{3 is} defined above.

Compound (7-i) → compound (16)

R ^b —CHO is usually used in an amount of 1 to 2 mol per 1 mol of compound (7-i).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; alcohols such as methanol, ethanol and isopropyl alcohol; and mixtures thereof.

Compound (16) → compound (7-v)

Sodium borohydride is usually used in an amount of 0.25 to 2 mol per 1 mol of compound (16).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; alcohols such as methanol, ethanol and isopropyl alcohol; and mixtures thereof.

Compounds (8-i), (8-ii) and (8-iii) are known compounds or can be prepared from known compounds by known methods (see, for example, Organic Functional Group Preparations, 2 ^nd edition, Vol. 1, chapter 14, p. 434-465, Stanley R. Sandler, Wolf Karo).

Compound (2) can be obtained by a method which, for example, is presented in the following scheme (8).

Scheme (8):

[Chemical formula 11]

where L ² represents a leaving group (e.g., a halogen atom, methylsulfonyl group and the like), L ³ represents a leaving group (e.g., methoxy group, ethoxy group, N, N-dimethylamino group, 1-imidazolyl group and the like), R ⁶ and R ^{7 are as} defined above.

Compound (13) → compound (2)

1. 3- (R ⁶ ) -substituted-1H-pyrazole is usually used in an amount of 1 mol per 1 mol of compound (13). Examples of the base used in this reaction include metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate; metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; and metal hydrides such as sodium hydride.

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; and mixtures thereof.

2. LDA (lithium diisopropylamide) is usually used in an amount of 1 mol, and compound (15) is usually used in an amount of 1 mol per 1 mol of 2- [3- (R ⁶ ) -substituted-1H-pyrazol-1-yl] -3 - (R ⁷ ) -substituted pyridine.

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; hydrocarbons such as toluene, benzene and xylene; and mixtures thereof.

Compound (13) is a known compound or can be obtained from a known compound in a known manner.

Compound (2) can also be obtained by a method which is presented, for example, in the following scheme (9).

Scheme (9):

[Chemical formula 12]

where R ^c represents a C1-C4 alkyl group, and R ⁶ and R ^{7 are} defined above.

Examples of the oxidizing agent used in the reaction include persulfates, such as sodium persulfate, potassium persulfate and ammonium persulfate. The oxidizing agent is usually used in an amount of from 1 to 2 mol per 1 mol of compound (17).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include nitriles, such as acetonitrile, water, and mixtures thereof.

Among the compounds (17), the compound represented by the formula (17-i) can be obtained, for example, according to the following scheme (10).

Scheme (10):

[Chemical formula 13]

where R ^d represents a methyl group, a phenyl group or a p-tolyl group, L ⁴ represents a chlorine atom or a bromine atom, X ¹ represents a halogen atom, and R ^c and R ^{7 are} defined above.

Compound (18) → compound (19)

Examples of HL ⁴ include hydrogen chloride and hydrogen bromide.

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and mixtures thereof.

Compound (19) → compound (20)

Examples of the chlorinating agent used in the reaction include oxalyl dichloride and thionyl chloride. The chlorinating agent is usually used in an amount of from 1 to 10 mol per 1 mol of compound (19).

The reaction is usually carried out in the absence of a solvent or in a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; and mixtures thereof.

Compound (20) → compound (22)

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; and mixtures thereof.

The amount of compound (21) used in the reaction is usually 1 mol per 1 mol of compound (20).

If necessary, the reaction is carried out in the presence of a base. If the reaction is carried out in the presence of a base, examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) and 1,5-diazabicyclo [ 4.3.0] -5-nonene (DBN), and tertiary amines such as triethylamine and N, N-diisopropylethylamine. If the reaction is carried out in the presence of a base, the base is usually used in an amount of 1 mol or more per 1 mol of compound (20).

Compound (18) → compound (23)

Examples of the chlorinating agent used in the reaction include oxalyl dichloride and thionyl chloride. The chlorinating agent is usually used in an amount of from 1 to 10 mol per 1 mol of compound (18).

The reaction is usually carried out in the absence of a solvent or in a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; and mixtures thereof.

Compound (23) → compound (24)

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; and mixtures thereof.

The amount of compound (21) used in the reaction is usually 1 mol per 1 mol of compound (23).

If necessary, the reaction is carried out in the presence of a base. If the reaction is carried out in the presence of a base, examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) and 1,5-diazabicyclo [ 4.3.0] -5-nonene (DBN); and tertiary amines such as triethylamine and N, N-diisopropylethylamine. If the reaction is carried out in the presence of a base, the base is usually used in an amount of 1 mol or more per 1 mol of compound (23).

Compound (24) → Compound (22)

Examples of HL ⁴ include hydrogen chloride and hydrogen bromide.

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and mixtures thereof.

Compound (22) → compound (25)

The reaction is carried out in the presence of a base. Examples of the base used in the reaction include metal carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, calcium carbonate and cesium carbonate. The base is usually used in an amount of 1 mol or more per 1 mol of compound (22).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; and mixtures thereof.

Compound (25) → compound (26)

Examples of the halogenating agent used in the reaction include oxalyl dichloride, thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, thionyl bromide, phosphorus bromide and phosphorus pentabromide. The halogenating agent is usually used in an amount of 1 to 10 mol per 1 mol of compound (25).

The reaction is usually carried out in the absence of a solvent or in a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; and mixtures thereof.

Compound (25) → Compound (27)

Examples of Cl-SO ₂ R ^d include methanesulfonyl chloride, benzenesulfonyl chloride and p-toluenesulfonyl chloride. Cl-SO ₂ R ^{d is} usually used in an amount of 1 mol per 1 mol of compound (25).

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; nitriles such as acetonitrile; aprotic polar solvents such as N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and dimethyl sulfoxide; and mixtures thereof.

If necessary, the reaction is carried out in the presence of a base. If the reaction is carried out in the presence of a base, examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) and 1,5-diazabicyclo [ 4.3.0] -5-nonene (DBN); and tertiary amines such as triethylamine and N, N-diisopropylethylamine. If the reaction is carried out in the presence of a base, the amount of base used is usually 1 mol or more per 1 mol of compound (25).

Compound (27) → compound (26)

Examples of HX ² include hydrogen chloride and hydrogen bromide.

The reaction is usually carried out in the presence of a solvent. Examples of the solvent include ethers such as 1,4-dioxane, diethyl ether and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, methylene bromide, chloroform, bromoform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; carboxylic acids such as acetic acid; and mixtures thereof.

Compound (26) → compound (17-i)

Examples of the oxidizing agent used in the reaction include persulfates, such as sodium persulfate, potassium persulfate and ammonium persulfate; quinone compounds such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), tetrachloro-1,4-benzoquinone (p-chloroanil), tetrabrom-1,4-benzoquinone (p-bromoanil ), tetrachloro-1,2-benzoquinone (o-chloroanil) and tetrabrom-1,2-benzoquinone (o-bromanil); halogens such as chlorine and bromine; and air.

If the oxidizing agent is persulfate, the amount of this oxidizing agent is usually from 1 to 2 mol per 1 mol of compound (26). Examples of the solvent commonly used in the reaction include nitriles, such as acetonitrile; water and mixtures thereof.

If the oxidizing agent is a quinone compound, the amount of this oxidizing agent is usually from 1 to 2 mol per 1 mol of compound (26). Examples of the solvent commonly used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran and methyl tert-butyl ether; halogen-containing hydrocarbons such as methylene chloride, methylene bromide, chloroform, bromoform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as hexane, heptane, toluene, benzene and xylene; nitriles such as acetonitrile; amides, such as N, N-dimethylformamide; nitrogen-containing cyclic compounds such as N-methylpyrrolidone and 1,3-dimethyl-2-imidazolidinone; aprotic polar solvents, for example sulfoxide solvents such as dimethyl sulfoxide; carboxylic acids such as acetic acid; ketones such as acetone and isobutyl methyl ketone; esters such as ethyl acetate; alcohols such as 2-propanol and tert-butyl alcohol; and water. A mixture of two or more solvents can be used, and the reaction can be carried out in a single phase system or in a two phase system.

If the oxidizing agent is halogen, the reaction is carried out in the presence of a solvent and a base, if necessary. The amount of oxidizing agent is usually from 1 mol to excess per 1 mol of compound (26). Examples of the solvent commonly used in the reaction include halogen-containing hydrocarbons such as methylene chloride, methylene bromide, chloroform, bromoform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and mixtures thereof. Examples of the base used include metal carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, calcium carbonate and cesium carbonate. The base is usually used in an amount of 1 mol or more per 1 mol of compound (26).

In the case where the oxidizing agent is air, the reaction is carried out in the presence of a solvent and a catalyst, if necessary. Examples of the solvent commonly used in the reaction include halogen-containing hydrocarbons such as methylene chloride, methylene bromide, chloroform, bromoform, carbon tetrachloride, 1,2-dichloroethane and chlorobenzene; hydrocarbons such as toluene, benzene and xylene; and mixtures thereof. Examples of the catalyst include metal halides such as iron (III) chloride and iron (III) bromide. The amount of catalyst used is usually from 0.001 mol to 1 mol per 1 mol of compound (26).

The above-described compound (1), compound (2) and their intermediates can be isolated and purified by a standard method, such as liquid separation, filtration, recrystallization, column chromatography, high-performance column chromatography (HPLC), preparative HPLC medium pressure, column chromatography on desalting resin, reprecipitation or distillation.

Next, each substituent represented by R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ in compound (1), compound (2) and compound (3) will be explained.

Examples of a “halogen atom” include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

Examples of a “C1-C6 alkyl group optionally substituted with at least one halogen atom” include a methyl group, a trifluoromethyl group, a trichloromethyl group, a chloromethyl group, a dichloromethyl group, a fluoromethyl group, a difluoromethyl group, an ethyl group, a pentafluoroethyl group, 2.2 , 2-trifluoroethyl group, 2,2,2-trichloroethyl group, propyl group, isopropyl group, heptafluoroisopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group and a hexyl group.

Examples of the “C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom” include a 2-methoxyethyl group, 2-ethoxyethyl group and 2-isopropyloxyethyl group.

Examples of the “C2-C6 alkenyl group optionally substituted with at least one halogen atom” include a 2-propenyl group, 3-chloro-2-propenyl group, 2-chloro-2-propenyl group, 3,3-dichloro-2 -propenyl group, 2-butenyl group, 3-butenyl group, 2-methyl-2-propenyl group, 3-methyl-2-butenyl group, 2-pentenyl group and 2-hexenyl group.

Examples of the “C3-C6 alkynyl group optionally substituted with at least one halogen atom” include a 2-propynyl group, 3-chloro-2-propynyl group, 3-bromo-2-propynyl group, 2-butynyl group and 3- butynyl group.

Examples of a “C1-C6 alkoxy group optionally substituted with at least one halogen atom” include a methoxy group, an ethoxy group, a 2,2,2-trifluoroethoxy group, a propoxy group, an isopropyloxy group, a butoxy group, an isobutoxy group, a sec-butoxy group and a tert-butoxy group.

Examples of the "C1-C6 alkylthio group optionally substituted by at least one halogen atom" include methylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, vtorbutiltiogruppu, tretbutiltiogruppu, pentylthio and hexylthio.

Examples of the “C1-C6 alkylsulfinyl group optionally substituted by at least one halogen atom” include a methylsulfinyl group, a trifluoromethylsulfinyl group, an ethylsulfinyl group, a propylsulfinyl group, an isopropylsulfinyl group, a butylsulfinyl group, an isobutylsulfinyl group, p-butylbutylbutylbutylbutylbutylbutyl group hexylsulfinyl group.

Examples of the "C1-C6 alkylsulfonyl group optionally substituted by at least one halogen atom" include a methylsulfonyl group, a trifluoromethylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylsulfonyl group, butylsulfonyl group, isobutylsulfonyl group, vtorbutilsulfonilnuyu group tretbutilsulfonilnuyu group, a pentylsulfonyl group and hexylsulfonyl group.

Examples of the compound (1) include the following compounds:

the compound of formula (1), where R ² represents a C1-C6 alkyl group, optionally substituted by at least one halogen atom;

the compound of formula (1), where R ² represents a hydrogen atom;

the compound of formula (1), where R ¹ represents a methyl group or ethyl group, and R ² represents a hydrogen atom, methyl group or ethyl group;

the compound of formula (1), where R ¹ and R ² represent methyl groups;

the compound of formula (1), where R ¹ represents a methyl group, and R ² represents a hydrogen atom;

the compound of formula (1), where R ¹ represents an ethyl group, and R ² represents a hydrogen atom;

a compound of formula (1), wherein R ³ is a C1-C6 alkyl group optionally substituted with at least one halogen atom;

the compound of formula (1), where R ³ represents a methyl group or ethyl group;

the compound of formula (1), where R ⁴ represents a halogen atom or an ethyl group;

the compound of formula (1), where R ⁵ represents a halogen atom or a cyano group;

the compound of formula (1), where R ⁴ represents a halogen atom or a methyl group, and R ⁵ represents a halogen atom or a cyano group;

the compound of formula (1), where R ¹ represents a methyl group or ethyl group, R ² represents a hydrogen atom, methyl group or ethyl group, R ³ represents a methyl group or ethyl group, R ⁴ represents a halogen atom or methyl group, and R ⁵ represents a halogen atom or a cyano group;

the compound of formula (1), where R ¹ , R ² and R ³ represent methyl groups, R ⁴ represents a chlorine atom, a bromine atom or a methyl group, and R ⁵ represents a chlorine atom, a bromine atom or a cyano group;

the compound of formula (1), where R ¹ represents a methyl group, R ² represents a hydrogen atom, R ³ represents a methyl group, R ⁴ represents a chlorine atom, a bromine atom or a methyl group, and R ⁵ represents a chlorine atom, an atom bromine or cyano; and

the compound of formula (1), where R ¹ represents an ethyl group, R ² represents a hydrogen atom, R ³ represents a methyl group, R ⁴ represents a chlorine atom, a bromine atom or a methyl group, and R ⁵ represents a chlorine atom, an atom bromine or cyano group.

Examples of the compound (2) include the following compounds:

the compound of formula (2), where R ⁶ represents a halogen atom or a C1-C6 alkyl group, optionally substituted by at least one halogen atom;

the compound of formula (2), where R ⁶ represents a halogen atom or a trifluoromethyl group;

the compound of formula (2), where R ⁷ represents a halogen atom;

the compound of formula (2), where R ⁶ represents a halogen atom or a trifluoromethyl group, and R ⁷ represents a halogen atom; and

the compound of formula (2), where R ⁶ represents a chlorine atom, a bromine atom or a trifluoromethyl group, and R ⁷ represents a chlorine atom.

Examples of the compound (3) include the following compounds:

the compound of formula (3), where R ² represents a C1-C6 alkyl group, optionally substituted by at least one halogen atom;

the compound of formula (3), where R ² represents a hydrogen atom;

the compound of formula (3), where R ¹ represents a methyl group or ethyl group, and R ² represents a hydrogen atom, methyl group or ethyl group;

the compound of formula (3), where R ¹ and R ² represent methyl groups;

the compound of formula (3), where R ¹ represents a methyl group, and R ² represents a hydrogen atom;

the compound of formula (3), where R ¹ represents an ethyl group, and R ² represents a hydrogen atom;

a compound of formula (3), wherein R ³ is a C1-C6 alkyl group optionally substituted with at least one halogen atom;

the compound of formula (3), where R ³ represents a methyl group or ethyl group;

the compound of formula (3), where R ⁴ represents a halogen atom or a methyl group;

the compound of formula (3), where R ⁵ represents a halogen atom or a cyano group;

the compound of formula (3), where R ⁴ represents a halogen atom or a methyl group, and R ⁵ represents a halogen atom or a cyano group;

the compound of formula (3), where R ⁶ represents a halogen atom or a C1-C6 alkyl group, optionally substituted by at least one halogen atom;

the compound of formula (3), where R ⁶ represents a halogen atom or a trifluoromethyl group;

the compound of formula (3), where R ⁷ represents a halogen atom;

the compound of formula (3), where R ⁶ represents a halogen atom or a trifluoromethyl group, and R ⁷ represents a halogen atom;

the compound of formula (3), where R ¹ represents a methyl group or an ethyl group, R ² represents a hydrogen atom, a methyl group or an ethyl group, R ³ represents a methyl group or an ethyl group, R ⁴ represents a halogen atom or a methyl group, R ⁵ represents a halogen atom or a cyano group, R ⁶ represents a halogen atom or a trifluoromethyl group, and R ⁷ represents a halogen atom;

the compound of formula (3), where R ¹ , R ² and R ³ represent methyl groups, R ⁴ represents a chlorine atom, a bromine atom or a methyl group, R ⁵ represents a chlorine atom, a bromine atom or a cyano group, R ⁶ represents an atom chlorine, a bromine atom or a trifluoromethyl group, and R ⁷ represents a chlorine atom;

the compound of formula (3), where R ¹ represents a methyl group, R ² represents a hydrogen atom, R ³ represents a methyl group, R ⁴ represents a chlorine atom, a bromine atom or a methyl group, R ⁵ represents a chlorine atom, a bromine atom or a cyano group, R ⁶ represents a chlorine atom, a bromine atom or a trifluoromethyl group, and R ⁷ represents a chlorine atom; and

the compound of formula (3), where R ¹ represents an ethyl group, R ² represents a hydrogen atom, R ³ represents a methyl group, R ⁴ represents a chlorine atom, a bromine atom or a methyl group, R ⁵ represents a chlorine atom, a bromine atom or a cyano group, R ⁶ represents a chlorine atom, a bromine atom or a trifluoromethyl group, and R ⁷ represents a chlorine atom.

Examples of the compound (17) include the following compounds:

the compound of formula (17), where R ⁶ represents a halogen atom or a C1-C6 alkyl group, optionally substituted by at least one halogen atom;

the compound of formula (17), where R ⁶ represents a halogen atom or a trifluoromethyl group;

the compound of formula (17), where R ⁷ represents a halogen atom;

the compound of formula (17), where R ⁶ represents a halogen atom or a trifluoromethyl group, and R ⁷ represents a halogen atom;

the compound of formula (17), where R ⁶ represents a chlorine atom, a bromine atom or a trifluoromethyl group, and R ⁷ represents a chlorine atom.

The compound (3) obtained by the method of the present invention has excellent regulatory activity against harmful arthropods. Examples of harmful arthropods that can be controlled using compound (3) include the following arthropods.

Semi-winged:

Delphacids such as the dark cicadas (Laodelphax striatellus), brown rice cicadas (Nilaparvata lugens) and white-backed rice fleas (Sogatella furcifera),

Cicadas such as green rice cicadas (Nephotettix cincticeps), green rice cicadas (Nephotettix virescens) and tea green cicadas (Empoasca onukii),

Vegetable aphids such as cotton aphids (Aphis gossypii), green peach aphids (Myzus persicae), cabbage aphids (Brevicoryne brassicae), spirae aphids (Aphis spiraecola), potato aphids (Macrosiphum euphorbiae), European common aphid (Aphis solum) aphids (Rhopalosiphum padi), tropical citrus aphids (Toxoptera citricidus) and plum pollinated aphids (Hyalopterus pruni),

Shield bugs, such as the cotton-garden bug (Nezara antennata), the bean bug (Riptortus clavetus), the rice bug (Leptocorisa chinensis), the white-spotted bug (Eysarcoris parvus), and the bug-bug (Halyomorpha mista),

Whiteflies, such as the greenhouse whitefly (Trialeurodes vaporariorum), cotton whitefly (Bemisia tabaci), magnolia whitefly (Bemisia argentifolii), citrus whitefly (Dialeurodes citri) and barbed citrus whitefly (Aleoruscantus)

Scalpidae, such as the orange-red scale insect (Aonidiella aurantii), the Californian scale insect (Comstockaspis perniciosa), the oriental citrus scale insect (Unaspis citri), the ruby rosacea (Ceroplastes rubens), the Australian grooved scorpion (Icerya Planococchae, Japanese) mealybug mealybug (Pseudococcus longispinis) and mulberry shield (Pseudalacaspis pentagona),

Lacemakers, leaf flocks and so on.

Butterflies:

Ognevka, such as a stem rice ridge (Chilo suppressalis), yellow rice ridge (Tryporyza incertulas), rice ridge (Cnaphalocrocis medinalis), cotton otne (Notarcha derogata), southern barn ogne (Plodia interpunctella), cornmeal, cornalrin cabbage (Hellula undalis) and ognevka (Pediasia teterrellus),

Lepidoptera, such as Asian cotton scoop (Spodoptera litura), small land scoop (Spodoptera exigua), rice scoop (Pseudaletia separata), cabbage scoop (Mamestra brassicae), ipsilon scoop (Agrotis ipsilon), beetroot scoop (nigra) Thoricoplusia species, Heliotis species and Helicoverpa species,

White butterfly butterflies, such as female repens (Pieris rapae),

Leafworms, such as the Adoxophyes species, the eastern moth (Grapholita molesta), the soya moth (Leguminivora glycinivorella), the caterpillar of the scoop of azuki beans (Matsumuraeses azukivora), the leaflet of summer fruit trees (Adoxophyes orana fasciata), the small tea species (oriental tea) leafworm (Homona magnanima), apple leafworm (Archips fuscocupreanus) and apple moth (Cydia pomonella),

Lepidoptera, such as the tea leaf (Caloptilia theivora) and apple moth miner (Phyllonorycter ringoneella),

Carposinides, such as the peach moth (Carposina niponensis),

Tiny moths, such as the species Lyonetia,

Excipients such as the Lymantria species and the Euproctis species,

Ermine moles, such as cabbage moth (Plutella xylostella),

Sagittarius moths, such as the pink cotton boxworm (Pectinophora gossypiella) and the potato tubule (Phthorimaea operculella),

Dipper, such as the American white butterfly (Hyphantria cunea),

The moles are real, such as a clear moth (Tinea translucens) and a clothes moth (Tineola bisselliella), and so on.

Bubbles:

Thrips such as yellow citrus thrips (Frankliniella occidentalis), palm thrips (Thrips palmi), Chilean yellow tea thrips (Scirtothrips dorsalis), tobacco thrips (Thrips tabaci) and wheat thrips (Frankliniella intonsa);

Two winged:

Housefly (Musca domestica), Common Mosquito (Culex popiens pallens), Horsefly (Tabanus trigonus), Onion fly larva (Hylemya antigua), Sprout fly larva (Hylemya platura), Anopheles sinensis, Rice miner (Agromyza oryzae, Hydrellia griseola), rice fly larva (Chlorops oryzae), melon fly (Dacus cucurbitae), Mediterranean fruit fly (Ceratitis capitata), American clover miner (Liriomyza trifolii), tomato leaf miner (Liriomyza sativae), miner leaf miner ) and so on.

Beetles:

Twenty-eight-dotted ladybug (Epilachna vigintioctopunctata), pumpkin leaf beetle (Aulacophora femoralis), striped flea beetle (Phyllotreta striolata), rice leaf beetle (Oulema oryzae), weevil rice weevil (Echinocnemusomusususususususususus squus grandis), azuki bean weevil (Callosobruchus chinensis), hunter weevil (Sphenophorus venatus), Japanese hrushchik (Popillia japonica), copper hrushka (Anomala cuprea), long-louse flea (Diabrotica species), Colorado beetle (leptinotidae), leptinotidae, (species Agriotes), tobacco beetle (Lasioderma serricorne), bark beetle (Anthrenus verbasci), chestnut cutter th (Tribolium caastaneum), hood (Lyctus brunneus), Asian barbel (Anoplophora malasiaca), large pine beetle (Tomicus piniperda) and so on;

Orthoptera:

Asian Migratory Locust (Locusta migratoria), African Bear (Gryllotalpa africana), Rice Filly (Oxya yezoensis), Rice Filly (Oxya japonica) and so on;

Hymenoptera:

Rapeseed sawfly (Athalia rosae), leaf ant (species Acromyrmex), fire ant (species Solenopsis) and so on;

Cockroaches:

Red cockroach (Blatella germanica), smoky brown cockroach (Periplaneta fuliginosa), American cockroach (Periplaneta americana), brown cockroach (Periplaneta brunea), black cockroach (Blatta orientalis) and so on;

Ticks:

Spider mites, such as the two-spotted spider mite (Tetranychus urticae), the Kansawa spider mite (Tetranychus kanzawai), the citrus red mite (Panonychus citri), the European red mite (Panonychus ulmi), and the species Oligonychus;

Gall four-legged ticks such as pink citrus gall mite (Aculops pelekassi), pink citrus gall mite (Phyllocoptruta citri), tomato pink mite (Aculops lycopersici), purple tea mite (Calacarus carinatus), pink gag tea gagapella and gall mite (Eriophyes chibaensis),

Tarsonelids, such as the greenhouse transparent tick (Polyphagotarsonemus latus),

Flat ticks such as Brevipalpus phoenicis,

Tukerelidovye,

Ixodes such as Haemaphysalis longicornis, Haemaphysalis flava, Dermacentor taiwanicus, Ixodes ovatus, Ixodes persulcatus, Boophilus microplus and Rhipicephalus sanguines,

Barn ticks such as Tyrophagus putrescentiae and Tyrophagus similes,

Pyroglyphide, such as Dermatophagoides farinae and Dermatophagoides ptrenyssnus,

Cheyletide, such as Cheyletus eruditus, Cheyletus malaccensis and Cheyletus moorei,

Dermanisside.

When using compound (3) as an agent for controlling harmful arthropods, although compound (3) can be used on its own, compound (3) is usually mixed with an inert carrier such as a solid carrier, a liquid carrier or a gaseous carrier, and furthermore , if necessary, with a surfactant and other pharmaceutical additives, to obtain an emulsifiable concentrate, solution in oil, powder, granules, wettable powder, flowable preparation, microcapsules, aerosol, fumigant, poisoned Anki, a resin-based preparation or the like, and then used. The composition thus obtained typically contains from 0.01 to 95% by weight of the compound (3).

Examples of the solid support used for the composition include fine powder or clay granules (kaolin clay, diatomaceous earth, bentonite, Fubazami clay, acid clay, etc.), synthetic hydrated silica, talc, ceramics, and other inorganic minerals (sericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica and the like), chemical fertilizers (ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride and the like) and so on.

Examples of a liquid carrier include water, alcohols (methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, propylene glycol, phenoxyethanol and so on), ketones (acetone, methyl ethyl ketone, cyclohexanone and so on), aromatic hydrocarbons (toluene, xylene , ethylbenzene, dodecylbenzene, phenylxylethylene, methylnaphthalene and so on), aliphatic hydrocarbons (hexane, cyclohexane, kerosene, gas oil and so on), esters (ethyl acetate, butyl acetate, isopropyl myristate, ethyl oleate, diisopropyl adipate, diisopropyl adipate, di propylene glycol monomethyl ether cetate and so on), nitriles (acetonitrile, isobutyronitrile and so on), ethers (diisopropyl ether, 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol glycol monomethyl ether, diethylene glycol glycol monomethyl ether, diethylene glycol glycol monomethyl ether, , 3-methoxy-3-methyl-1-butanol and so on), acid amides (N, N-dimethylformamide, N, N-dimethylacetamide and so on), halogen-containing hydrocarbons (methylene chloride, trichloroethane, carbon tetrachloride and etc ), sulfoxides (dimethyl sulfoxide and so on), propylene carbonate and vegetable oils (soybean oil, cottonseed oil and so on).

Examples of a gaseous carrier include fluorocarbon, gaseous butane, LPG (liquefied associated gas), dimethyl ether and gaseous carbon dioxide.

Examples of the surfactant include nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether and polyethylene glycol fatty acid ester, and anionic surfactants such as alkyl sulfonate, alkyl benzene sulfonate and alkyl sulfate.

Examples of other pharmaceutical additives include a binder, dispersant, dye, and stabilizer, and specific examples thereof include casein, gelatin, saccharides (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, synthetic water-soluble polymers (polyvinyl alcohol) , polyvinylpyrrolidone, polyacrylic acid and so on), PAP (acidic isopropyl phosphate), BHT (2,6-ditretbutyl-4-methylphenol) and BHA (a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol).

To combat harmful arthropods, compound (3) can be used on its own. Typically, a harmful arthropod control agent described above containing the compound (3) is used to control harmful arthropods. A method for controlling harmful arthropods includes the use of a compound (3) or an agent for controlling harmful arthropods containing a compound (3) to harmful arthropods or to the habitat of harmful arthropods, by analogy with the method used to apply the known pesticide.

Examples of habitats for harmful arthropods include rice fields, cropland, orchards, non-cropland, and houses.

Examples of the method of application include spray treatment, soil treatment, grain processing and treatment of the aquatic culture medium.

Spraying is a treatment method comprising treating the surface of the plants or the harmful arthropods themselves with the active ingredient and, due to this, can have a regulatory effect on the harmful arthropods. Specific examples of spray treatment include spraying foliage, spraying tree trunks, and so on.

Tillage is a treatment method that includes treating the soil or irrigation fluid with the active ingredient to allow the active ingredient to penetrate and transfer into the stem of the crop plant that needs to be protected from damage, such as being eaten by harmful arthropods, through the root or similar part of the plant, and Thus, it can protect the crop from damage by harmful arthropods. Specific examples of soil cultivation include treatment of planting holes (spraying into planting holes, mixing the soil after treatment of planting holes), treating the roots of the plant (spraying on the roots of the plant, mixing the soil after treating the roots of the plant, irrigating the roots of the plant at a later stage of cultivation), processing furrows for planting (spraying on furrows for planting, mixing the soil after processing furrows for planting), processing rows for planting (spraying on rows for planting , mixing the soil after processing the rows for planting, spraying on the rows for planting at the growth stage), processing the rows for planting during sowing (spraying on the rows for planting during sowing, mixing the soil after processing the rows for planting during sowing), spreading (general spraying onto the surface of the soil, mixing of the soil after spreading), other spraying of the soil (spraying a granular preparation on the foliage at the growth stage, spraying under the crown or around the trunk wood, spraying on the soil surface, mixing with the soil surface, spraying in the holes for seeds, spraying on the ground surface of the furrows, spraying between plants), other irrigation treatment (irrigation of the soil, irrigation at the stage of germination of sprouts, treatment by infusion of a solution of the drug, irrigation of part of the plant directly above the ground, drip irrigation with a solution of a preparation, chemicalization), treatment of a seedling box (spraying in a seedling box, irrigation of a seedling box), processing of a seedling tray (spraying in seedling tray, seedling tray irrigation), processing of beds (spraying on beds, irrigation of beds, spraying in lowland rice seedlings, dipping seedlings), soil cultivation of beds by introduction (mixing with soil of beds, mixing with soil of beds before sowing) and other processing (mixing with cultivated soil, for plowing, mixing with surface soil, mixing with soil at the place where the raindrops fall from the crown, processing at the planting site, spraying the granular preparation into clusters of flowers, mixing with pasty obreniem).

Seed dressing is a treatment method that involves applying the active ingredient directly to a seed, seed tuber or seed bulb that needs to be protected from damage, such as being eaten by or around harmful arthropods, and thus may have a regulatory effect on harmful arthropods. Specific examples of seed dressing include a spray treatment, a spray coating treatment, an immersion treatment, an impregnation treatment, a coating treatment, a film coating treatment, and a granulation treatment.

The treatment of an aqueous culture medium is a treatment method that includes treating an aqueous culture medium or the like with an active ingredient to allow penetration and transfer of the active ingredient into the interior of the plant that needs to be protected from damage, such as being eaten by harmful arthropods through the root of the plant or the like, and thus can protect the crop from being harmed by harmful arthropods. Specific examples of treatment of an aqueous culture medium include mixing with an aqueous culture medium and introducing into an aqueous culture medium.

In the case where an agent for controlling harmful arthropods containing compound (3) is used to control harmful arthropods in the agricultural field, it is usually used in an amount of 1 to 10,000 g of compound (3) per 10,000 m ² . If an emulsifiable concentrate, wettable powder, or a flowable formulation is prepared on the basis of an anti-arthropod control agent, the harmful arthropod control agent is usually used after it has been dissolved in water so that the concentration of the active ingredient is from 0.01 to 10,000 hours ./mln If a formulation in the form of a granule or powder is obtained on the basis of an agent for controlling harmful arthropods, the agent for controlling harmful arthropods is usually used as it is.

The harmful arthropod control agent or an aqueous solution of the harmful arthropod control agent can be directly sprayed onto the harmful arthropods or plants, such as crops that need to be protected from the harmful arthropods. Alternatively, the soil of the treated land can be treated with an agent for controlling harmful arthropods or an aqueous solution of an agent for controlling harmful arthropods in order to destroy the harmful arthropods inhabiting the soil.

The agent for controlling harmful arthropods may take the form of a polymer composition that is processed to produce a sheet or thread. Such a polymer composition can be used by wrapping a plant with a sheet or strand of polymer composition, placing a strand of polymer composition around the plant so that the plant is surrounded by this thread, or laying a sheet of polymer composition on the soil surface near the root of the plant.

In the case where an agent for controlling harmful arthropods containing compound (3) is used to control harmful arthropods living in a house (e.g., a fly, mosquito, cockroach), it is usually used in an amount of from 0.01 to 1000 mg of the compound ( 3) per 1 m ² in the case of processing a flat surface, and usually from 0.01 to 500 mg of compound (3) per 1 m ³ in the case of processing the space. If, based on the harmful arthropod control agent containing compound (3), an emulsifiable concentrate, wettable powder or flowable powder is obtained, the harmful arthropod control agent is usually used after it is dissolved in water so that the concentration of the active ingredient is from 0, 1 to 1000 ppm If, based on the harmful arthropod control agent containing compound (3), a composition is obtained in the form of a solution in oil, an aerosol, a fumigant, or a poison bait, the harmful arthropod control agent is used in the form in which it is.

Compound (3) can be used as an insecticide for sown land, such as cultivated land, rice fields, lawns and orchards, or for non-sown land. In some cases, using the compound obtained by the method of the present invention, it is possible to control pests on sown lands and so on, where the following crops and the like are grown without causing harm to these crops.

Crops: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soy, peanuts, semi-umbrella buckwheat, sugar beets, rape, sunflower, sugarcane, tobacco and so on;

Vegetables: plants of the nightshade family (eggplant, tomato, green pepper, capsicum, potatoes and so on), gourds (cucumber, pumpkin, zucchini, watermelon, melon and so on), cruciferous plants (Japanese radish, turnip, horseradish, kohlrabi , Chinese cabbage, cabbage, Chinese mustard, broccoli, cauliflower and so on), asteraceae plants (burdock, edible chrysanthemum, artichoke, lettuce and so on), lily plants (spring onion, onion, garlic, asparagus and so on), umbrella plants (carrots, parsley, celery, parsnip and so on lee), haze plants (spinach, Swiss chard and so on), labio plants (Japanese basil, mint, basil and so on), strawberries, sweet potatoes, yams, aroid and so on;

Flowers;

Ornamental plants;

Fruit trees: apple-like fruits (apple, common pear, Chinese quince, quince and so on), pitted fleshy fruits (peach, plum, nectarine, Japanese plum, cherry, apricot, prune and so on), citrus plants (Satsumi mandarin, orange , lemon, lime, grapefruit and so on), nuts (chestnut, walnut, hazelnuts, almonds, pistachio, cashews, macadamia nuts and so on), berries (blueberries, cranberries, blackberries, raspberries and so on), vine persimmon, olive, lokva, banana, coffee, date, coconut and so on;

Trees other than fruit trees: tea, mulberry, flowering trees and shrubs, urban trees (ash, birch, dogwood, eucalyptus, gingko, lilac, maple tree, oak, poplar, tsertsis, Chinese amber tree, plane tree, zelkva, Japanese thuja , fir, Japanese tsuga, solid juniper, pine, spruce, yew) and so on.

Hereinafter, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to them.

Examples

Example 1

A mixture of 0.79 g of compound (1-1):

[Chemical formula 14]

,

,

0.57 g of compound (2-1):

[Chemical formula 15]

,

,

0.04 g of p-toluenesulfonic acid monohydrate and 10 ml of toluene were stirred and heated under reflux in air for 3 hours. After the reaction mixture was cooled to room temperature, water was poured into the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.20 g of compound (3-1).

Compound (3-1):

[Chemical formula 16]

¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.71 (1.4H, s), 2.83 (1.6H, s), 2.94 (1.5H, s), 3.06 (1.5H, s), 3.35-3.70 (3.0H, m), 7.41 (0.5H, s), 7.45 (0.6H, s) 7.47 (0.6H, s), 7.60-7.64 (1.3H, m), 8.07 (0.5H, d, J = 2 Hz), 8.13 (0.5H , s), 8.18 (1.0H, d, J = 8 Hz), 8.50 (1.0H, m), 10.52 (0.5H, s), 10.67 (0.5H, from).

Example 2

A mixture of 0.25 g of compound (1-1), 0.18 g of compound (2-1), 1 mg of copper (I) iodide, 0.12 g of m-chloroperbenzoic acid and 1 ml of acetonitrile was stirred and heated to reflux refrigerator under nitrogen for 7 hours. After the reaction mixture was cooled to room temperature, water was poured into the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.10 g of compound (3-1).

Example 3

A mixture of 0.30 g of compound (1-1), 0.22 g of compound (2-1), 0.33 g of pyridinium chlorochromate (PCC), p-toluenesulfonic acid monohydrate (catalytic amount) and 4 ml of chlorobenzene was stirred under a nitrogen atmosphere under 100 ° C for 1 hour. A sample was taken from the reaction mixture and subjected to TLC analysis (thin layer chromatography). As a result, the preparation of compound (3-1) was confirmed.

Example 4

To obtain compound (3-2), instead of compound (1-1) from Example 2, compound (1-2) was used:

[Chemical formula 17]

Compound (3-2):

[Chemical formula 18]

Example 5

To obtain compound (3-4), instead of compound (1-1) from Example 2, compound (1-4) was used:

[Chemical formula 19]

[Chemical formula 20]

Specific examples of compound (3), which can be obtained by the method of the present invention, are listed below.

Table 1 Connection number R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ R ⁷ 3-1 CH ₃ CH ₃ CH ₃ Br Br Br Cl 3-2 CH ₃ CH ₂ H CH ₃ Br Br Br Cl 3-3 CH ₃ H CH ₃ CH ₃ Cl Br Cl 3-4 CH ₃ H CH ₃ Br Br Br Cl 3-5 (CH ₃ ) ₂ CH H CH ₃ Br Br Br Cl 3-6 CH ₃ H CH ₃ CH ₃ Cl CF ₃ Cl 3-7 CH ₃ CH ₃ CH ₃ CH ₃ Cl Br Cl 3-8 CH ₃ H CH ₃ CH ₃ CN Br Cl 3-9 CH ₃ CH ₃ CH ₃ CH ₃ CN Br Cl 3-10 CH ₃ H CH ₃ Cl Cl Br Cl 3-11 CH ₃ H CH ₃ CH ₂ Cl Cl Br Cl 3-12 CH ₃ CH ₃ CH ₃ Cl Cl Br Cl 3-13 CH ₃ CH ₃ CH ₃ Br Cl Br Cl 3-14 CH ₃ CH ₃ CH ₃ CH ₃ Cl Cl Cl 3-15 CH ₃ CH ₃ CH ₃ Cl Cl Cl Cl 3-16 CH ₃ CH ₃ CH ₃ Br Br Cl Cl 3-17 CH ₃ CH ₂ H CH ₃ Cl Cl Br Cl 3-18 CH ₃ CH ₃ CH ₃ Br Br CF ₃ Cl 3-19 CH ₃ (CH ₂ ) ₂ H CH ₃ Br Br Br Cl 3-20 CH ₃ CH ₃ CH ₂ CH ₃ Br Br Br Cl 3-21 CH ₃ CH ₂ CH ₃ CH ₃ Br Br Br Cl 3-22 CH ₃ CH ₂ CH ₃ CH ₂ CH ₃ Br Br Br Cl

table 2 Connection number R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ R ⁷ 3-23 CH ₃ CH ₂ H CH ₃ CH ₃ Cl Br Cl 3-24 CH ₃ CH ₂ H CH ₃ CH ₃ CN Br Cl 3-25 CH ₃ CH ₂ H CH ₃ Br Br Cl Cl 3-26 CH ₃ CH ₂ H CH ₃ Cl Cl Cl Cl 3-27 CH ₃ CH ₂ H CH ₃ CH ₃ Cl Cl Cl 3-28 CH ₃ CH ₂ H CH ₃ CH ₃ CN Cl Cl 3-29 CH ₃ CH ₂ H CH ₃ Br Br CF ₃ Cl 3-30 CH ₃ CH ₂ H CH ₃ Cl Cl CF ₃ Cl 3-31 CH ₃ CH ₂ H CH ₃ CH ₃ Cl CF ₃ Cl 3-32 CH ₃ CH ₂ H CH ₃ CH ₃ CN CF ₃ Cl 3-33 CH ₃ H CH ₃ Br Br CF ₃ Cl 3-34 CH ₃ H CH ₃ Br Br Cl Cl 3-35 CH ₃ H CH ₃ Cl Cl Cl Cl 3-36 CH ₃ H CH ₃ CH ₃ Cl Cl Cl 3-37 CH ₃ H CH ₃ CH ₃ CN Cl Cl 3-38 CH ₃ H CH ₃ Cl Cl CF ₃ Cl 3-39 CH ₃ H CH ₃ CH ₃ CN CF ₃ Cl 3-40 CH ₃ CH ₃ CH ₃ CH ₃ CN Cl Cl 3-41 CH ₃ CH ₃ CH ₃ Cl Cl CF ₃ Cl 3-42 CH ₃ CH ₃ CH ₃ CH ₃ Cl CF ₃ Cl 3-43 CH ₃ CH ₃ CH ₃ CH ₃ CN CF ₃ Cl

The physical properties of some compounds are given (3).

Compound (3-1)

¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.71 (1.4H, s), 2.83 (1.6H, s), 2.94 (1.5H, s), 3.06 (1.5H, s), 3.35-3.70 (3.0H, m), 7.41 (0.5H, s), 7.45 (0.6H, s) 7.47 (0.6H, s), 7.60-7.64 (1.3H, m), 8.07 (0.5H, d, J = 2 Hz), 8.13 (0.5H , s), 8.18 (1.0H, d, J = 8 Hz), 8.50 (1.0H, m), 10.52 (0.5H, s), 10.67 (0.5H, from).

Compound (3-2)

¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 0.86 (1.0H, t, J = 7 Hz), 0.99 (2.0H, t, J = 7 Hz ), 3.10 (1.7H, br s), 3.50 (2.4H, s), 3.64 (0.6H, s), 3.85 (0.3H, br s), 7.36-7.44 (2.0H, m), 7.59-7.65 (1.0H, m), 8.07-8.21 (2.0H, m), 8.49-8 51 (1.0H, m), 9.04 (0.7H, br.s), 9.71 (0.3H, br.s), 10.30 (0.7H, br.s), 10 66 (0.3H, br s).

Compound (3-3)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 2.04 (3H, s), 3.22 (3H, s), 3.57 (2.6H, s), 3.80 (0.4H, s), 7.01 (1H, s), 7.04 (1H, s), 7.28 (1H, s), 7.40 (1H, dd, J = 8 Hz, 5 Hz ), 7.61 (1H, br.s), 7.87 (1H, dd, J = 8 Hz, 2 Hz), 8.46 (1H, dd, J = 5 Hz, 2 Hz), 9.80 (1H, broad s).

Compound (3-4)

¹ H-NMR (100 ° C, DMSO-d ₆ , TMS) δ (ppm): 2.96 (3H, s), 3.04 (3H, br s), 7.30 (1H, s), 7.38 (1H, s), 7.58 (1H, dd, J = 8 Hz, 5 Hz), 7.96 (1H, s), 8.11 (1H, d, J = 8 Hz ), 8.47 (1H, d, J = 5 Hz), 8.68 (1H, br.s), 10.08 (1H, br.s).

Compound (3-5)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 0.87-0.95 (3.8H, m), 1.13-1.26 (4.4H, m), 3, 55 (2.5H, s), 3.81 (0.5H, s), 4.55-4.67 (1.0H, m), 7.37-7.42 (3.0H, m), 7.49 (1.0H, d, J = 2 Hz), 7.57 (1.1H, d, J = 2 Hz), 7.86 (1.0H, dd, J = 8 Hz, 2 Hz) 8.45 (1.0H, dd, J = 5 Hz, 2 Hz), 9.68 (0.3H, br.s), 9.93 (0.7H, br.s).

Compound (3-6)

¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.11 (3H, s), 3.06 (3H, s), 3.33 (3H, s), 7.07 (1H, s), 7.45 (1H, s), 7.68 (1H, s), 7.69 (1H, dd, J = 8 Hz, 4 Hz), 8.24 (1H, d, J = 8 Hz), 8.55 (1H, d, J = 4 Hz), 9.11 (0.6H, br.s), 10.20 (1H, br.s), 10.54 (0.4H , ears.s).

Compound (3-7)

¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.10-2.24 (3H, m), 2.61-2.87 (3H, m), 2.90- 3.18 (3H, m), 3.45-3.74 (3H, m), 7.12-7.30 (1H, m), 7.33-7.44 (1H, m), 7, 44-7.58 (1H, m), 7.58-7.66 (1H, m), 8.20 (1H, d, J = 8Hz), 8.47-8.54 (1H, m), 10.10-10.50 (1H, m).

Compound (3-8)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.21 (3H, s), 3.08 (3H, s), 3.45-3.70 (3H, m) 7.30-7.43 (1H, m), 7.44-7.61 (1H, m), 7.63 (1H, dd, J = 8 Hz, 5 Hz), 7.82-7, 94 (1H, m), 8.21 (1H, d, J = 8 Hz, 1 Hz), 8.51 (1H, dd, J = 5 Hz, 1 Hz), 9.21 (1H, br.s ), 10.24 (1H, br s).

Compound (3-9)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.14-2.29 (3H, m), 2.64-2.87 (3H, m), 2.87- 3.15 (3H, m), 3.42-3.73 (3H, m), 7.30-7.45 (1H, m), 7.54-7.81 (2H, m), 7, 83-8.01 (1H, m), 8.15-8.24 (1H, m), 8.50 (1H, br.s), 10.20-10.68 (1H, m).

Compound (3-10)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 3.12-3.18 (3H, br.m), 3.60-3.84 (3H, br.m), 7, 21-7.22 (2H, m), 7.34 (1H, br.s), 7.41 (1H, dd, J = 8 Hz, 5 Hz), 7.51 (1H, br.s), 7.88 (1H, dd, J = 8 Hz, 1 Hz), 8.48 (1H, dd, J = 5 Hz, 1 Hz), 9.85 (1H, br.s).

Compound (3-11)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.11-1.39 (3H, m), 3.12-3.18 (3H, br.m), 4.06- 4.25 (2H, br.s.), 7.08-7.22 (2H, m), 7.34 (1H, br.s), 7.41 (1H, dd, J = 8 Hz, 5 Hz ), 7.43 (1H, br.s), 7.88 (1H, dd, J = 8 Hz, 1 Hz), 8.49 (1H, dd, J = 5 Hz, 1 Hz), 9.87 (1H, broad s).

Compound (3-12)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.73 (1.4H, s), 2.83 (1.6H, s), 2.95 (1.6H, s), 3.07 (1.4H, s), 3.49-3.68 (3.0H, m), 7.32-7.44 (2.0H, m), 7.62 (1, 0H, dd, J = 8 Hz, 5 Hz), 7.85 (0.5H, d, J = 2 Hz), 7.92 (0.5H, s), 8.19 (1.0H, dd, J = 8 Hz, 1 Hz), 8.49-8.52 (1.0H, m), 10.53 (0.5H, s), 10.71 (0.5H, s).

Compound (3-13)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.72 (1.4H, s), 2.83 (1.6H, s), 2.94 (1.6H, s), 3.07 (1.4H, s), 3.49-3.68 (3.0H, m), 7.34-7.45 (2.0H, m), 7.60-7, 64 (1.0H, m), 7.98 (0.4H, d, J = 2 Hz), 8.04 (0.5H, s), 8.19 (1.0H, d, J = 8 Hz ), 8.49-8.52 (1.0H, m), 10.54 (0.5H, s), 10.70 (0.5H, s).

Compound (3-14)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.13 (1.4H, s), 2.18 (1.6H, s), 2.73 (1.4H, s), 2.82 (1.6H, s), 2.93-2.96 (1.2H, m), 3.07-3.07 (1.8H, m), 3.43-3, 69 (3.0H, m), 7.18-7.32 (2.0H, m), 7.46-7.53 (1.0H, m), 7.60-7.64 (1.0H , m), 8.19 (1.0H, d, J = 8Hz), 8.49-8.51 (1.0H, m), 10.20 (0.4H, br.s), 10.45 (0.6H, br s).

Compound (3-15)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.73 (1.3H, s), 2.84 (1.7H, s), 2.95 (1.3H, br.s), 3.07-3.08 (1.7H, m), 3.46-3.68 (3.0H, m), 7.32-7.39 (2.0H, m), 7.62 (1.0H, dd, J = 8 Hz, 5 Hz), 7.85-7.92 (1.0H, m), 8.19 (1.0H, d, J = 8 Hz), 8 49-8.51 (1.0H, m), 10.54 (0.4H, br.s), 10.74 (0.6H, br.s).

Compound (3-16)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.71 (1.4H, s), 2.83 (1.6H, s), 2.94 (1.3H, br.s), 3.06-3.08 (1.7H, m), 3.44-3.68 (3.0H, m), 7.36-7.47 (2.0H, m), 7.60-7.64 (1.0H, m), 8.08-8.20 (2.0H, m), 8.50-8.51 (1.0H, m), 10.56 (0 4H, broad s), 10.71 (0.6H, broad s).

Compound (3-17)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.03-1.07 (3.0H, m), 3.31-3.82 (5.0H, m), 7, 23 (2.0H, s), 7.31 (1.0H, s), 7.39 (1.0H, dd, J = 8 Hz, 5 Hz), 7.54 (1.0H, s), 7.87 (1.0H, dd, J = 8 Hz, 1 Hz), 8.46 (1.0H, dd, J = 5, 1 Hz), 9.65 (0.2H, br.s), 9.86 (0.8H, br s).

Compound (3-18)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 2.71 (1.4H, s), 2.84 (1.6H, s), 2.95 (1.3H, br.s), 3.07 (1.7H, s), 3.45-3.70 (3.0H, br.m), 7.48 (1.0H, br.s), 7.66- 7.71 (1.0H, m), 7.77-7.80 (1.0H, m), 8.12 (1.0H, d, J = 21Hz), 8.24 (1.0H, dd , J = 8 Hz, 1 Hz), 8.53-8.55 (1.0H, m), 10.72 (0.4H, br.s), 10.85 (0.6H, br.s) .

Compound (3-19)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 0.88-0.95 (3H, m), 1.48 (2H, tq, J = 8 Hz, 8 Hz), 3 , 22-3.83 (5H, br.m), 7.37-7.44 (3H, m), 7.56 (1H, d, J = 2 Hz), 7.61 (1H, s), 7.86 (1H, dd, J = 8 Hz, 2 Hz), 8.46 (1H, dd, J = 5 Hz, 2 Hz), 9.77 (0.3H, s), 9.98 (0 , 7H, s).

Compound (3-20)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 0.79-1.00 (3.0H, m), 2.88 (2.2H, d, J = 12 Hz) 3.01-3.08 (1.0H, m), 3.12 (0.8H, s), 3.15-3.22 (1.0H, m), 3.45-3.69 ( 3.0H, m), 7.41-7.47 (2.0H, m), 7.60-7.64 (1.0H, m), 8.10-8.20 (2.0H, m ), 8.49-8.52 (1.0H, m), 10.50 (0.3H, br.s), 10.70 (0.7H, br.s).

Compound (3-21)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 0.86-0.91 (2.0H, m), 1.11-1.14 (1.0H, m), 2.75 (1.0H, s), 2.85-3.23 (4.0H, br.m), 3.64-3.73 (3.0H, m), 7.41-7.46 (2.0H, m), 7.60-7.63 (1.0H, m), 8.07-8.19 (2.0H, m), 8.48-8.50 (1.0H, m), 10.48 (0.3H, br.s), 10.67 (0.7H, br.s).

Compound (3-22)

¹ H-NMR (DMSO-d ₆ , TMC) δ (ppm): 0.86-1.15 (6.0H, br.m), 3.08-3.29 (3.0H, br m), 3.37-3.74 (4.0H, br.m), 7.43-7.47 (2.0H, m), 7.61-7.65 (1.0H, m) 8.10-8.20 (2.0H, m), 8.49-8.51 (1.0H, m), 10.47 (0.3H, br.s), 10.65-10, 76 (0.7H, broad m).

Compound (3-23)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.06 (3H, t, J = 7 Hz), 2.04 (3H, s), 3.56-3.78 (5H , m), 7.02 (1H, s), 7.06 (1H, s), 7.20-7.26 (1H, m), 7.38 (1H, dd, J = 8.5 Hz) 7.62 (1H, s), 7.86 (1H, dd, J = 8 Hz, 2 Hz), 8.44 (1H, dd, J = 5 Hz, 2 Hz), 9.82 (1H, ears.s).

Compound (3-25)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.04 (3H, t, J = 7Hz), 3.45-3.90 (5H, m), 7.23 (1H, s), 7.40 (1H, dd, J = 8 Hz, 5 Hz), 7.45 (1H, d, J = 2 Hz), 7.54 (1H, s), 7.60 (1H, d , J = 2 Hz), 7.87 (1H, dd, J = 8 Hz, 2 Hz), 8.46 (1H, dd, J = 5 Hz, 2 Hz), 9.67 (1H, br.s )

Compound (3-26)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.05 (3H, t, J = 7 Hz), 3.43-3.69 (5H, m), 7.19-7 , 22 (3H, m), 7.40 (1H, dd, J = 8 Hz, 5 Hz), 7.53 (1H, s), 7.87 (1H, d, J = 8 Hz), 8, 46 (1H, d, J = 5 Hz), 9.82 (1H, br.s).

Compound (3-27)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.06 (3H, t, J = 7Hz), 2.04 (3H, s), 3.45-3.95 (5H, m), 7.02 (1H, s), 7.06 (1H, s), 7.17 (1H, s), 7.38 (1H, dd, J = 8 Hz, 5 Hz), 7.63 (1H, s), 7.86 (1H, dd, J = 8 Hz, 2 Hz), 8.44 (1H, dd, J = 5 Hz, 2 Hz), 9.83 (1H, br.s) .

Compound (3-29)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.04 (3H, t, J = 7 Hz), 3.41-3.83 (5H, m), 7.42-7 45 (2H, m), 7.55-7.58 (2H, m), 7.70 (1H, s), 7.89 (1H, dd, J = 8 Hz, 2 Hz), 8.48 (1H, dd, J = 5 Hz, 2 Hz), 10.20 (1H, br.s).

Compound (3-30)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.05 (3H, t, J = 7 Hz), 3.45-3.95 (5H, m), 7.35 (1H , s), 7.39 (1H, dd, J = 8 Hz, 5 Hz), 7.43 (1H, d, J = 2 Hz), 7.55-7.59 (2H, m), 7, 86 (1H, dd, J = 8 Hz, 2 Hz), 8.46 (1H, dd, J = 5 Hz, 2 Hz), 9.86 (1H, br.s).

Compound (3-31)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 1.05 (3H, t, J = 7 Hz), 1.99 (3H, s), 3.45-3.95 (5H , m), 6.97 (1H, s), 7.04 (1H, s), 7.42 (1H, dd, J = 8 Hz, 5 Hz), 7.65 (1H, s), 7, 67 (1H, s), 7.88 (1H, d, J = 8 Hz), 8.46 (1H, d, J = 5 Hz), 10.27 (1H, br.s).

Compound (3-33)

¹ H-NMR (CDCl ₃ , TMC) δ (ppm): 3.18 (3H, s), 3.60-3.85 (3H, m), 7.42-7.46 (2H, m), 7.55-7.58 (2H, m), 7.72 (1H, s), 7.90 (1H, dd, J = 8 Hz, 2 Hz), 8.49 (1H, dd, J = 5 Hz, 2 Hz), 10.14 (1H, br.s).

Next, in the form of standard production examples, production examples of compound (1) and compound (2) will be described.

Example 1 standard preparation

(1) 6.0 g of 6.8-dibromo-2H-3,1-benzoxazine-2,4-1H-dione were added to a mixture of 1.85 g of methyl carbazate and 60 ml of tetrahydrofuran under ice cooling:

[Chemical formula 21]

(the compound is described in Journal of Organic Chemistry (1947), 12, 743-51), followed by stirring for 3 hours under ice-cooling. The reaction mixture was warmed to room temperature and another 0.46 g of methyl carbazate was added thereto. The mixture was stirred at room temperature for 15 hours, and then concentrated under reduced pressure. Water was poured into the obtained residue. The remaining precipitate was filtered off. This residue was washed successively with water and ethyl acetate to give 4.96 g of N- (2-amino-3,5-dibromobenzoyl) -N'-methoxycarbonylhydrazine.

N- (2-amino-3,5-dibromobenzoyl) -N'-methoxycarbonylhydrazine

¹ H-NMR (DMSO-d ₆ ) δ: 3.63 (3H, s), 6.55 (2H, s), 7.71 (1H, s), 7.79 (1H, s), 9, 25 (1H, s), 10.32 (1H, s).

(2) To a mixture of 3.67 g of N- (2-amino-3,5-dibromobenzoyl) -N'-methoxycarbonylhydrazine, 3.04 g of potassium carbonate and 50 ml of N-methylpyrrolidone was added dropwise a mixture of 3.12 g of methyl iodide and 2 ml of 1-methyl-2-pyrrolidinone under ice-cooling, after which it was stirred under ice-cooling for 4 hours, and then stirred at room temperature for 3 hours. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 2.83 g of compound (1-1).

Compound (1-1)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.11-3.18 (6H, m), 3.76 (3H, br s), 4.86 (1.4H, br.s), 5.23 (0.6H, br.s), 7.17-7.25 (1H, m), 7.57 (1H, d, J = 2 Hz).

Example 2 standard preparation

(1) To a mixture of 0.61 g of ethyl hydrazinoxalate, 1.0 g of 6.8-dibromo-2H-3,1-benzoxazine-2,4-1H-dione and 10 ml of tetrahydrofuran, 1.12 g of potassium carbonate was added under ice-cooling then stirred at room temperature for 1.5 hours. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed successively with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.44 g of N- (2-amino-3,5-dibromobenzoyl) -N-ethylhydrazine and 0.13 g of N- (2-amino-3,5-dibromobenzoyl) -N '-ethylhydrazine.

N- (2-amino-3,5-dibromobenzoyl) -N-ethylhydrazine

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.25 (3H, t, J = 7 Hz), 3.52 (2H, kV, J = 7 Hz), 4.38 (2H, br.s), 4.81 (2H, br.s), 7.21 (1H, d, J = 2 Hz), 7.59 (1H, d, J = 2 Hz).

N- (2-amino-3,5-dibromobenzoyl) -N'-ethylhydrazine

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.15 (3H, t, J = 7 Hz), 2.95 (2H, q, J = 7 Hz), 4.78 (1H, br.s), 6.02 (2H, br.s), 7.38 (1H, d, J = 2 Hz), 7.52 (1H, br.s), 7.64 (1H, d, J = 2 Hz).

(2) To a mixture of 0.42 g of N- (2-amino-3,5-dibromobenzoyl) -N-ethylhydrazine and 3 ml of pyridine was added 0.15 g of methyl chloroformate under ice-cooling, followed by stirring under ice-cooling for 1 hour . Water was poured into the reaction mixture, then concentrated under reduced pressure. Water was poured into the obtained residue, after which it was extracted with ethyl acetate. The organic layer was washed successively with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.42 g of compound (1-2).

Compound (1-2)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.21 (3H, t, J = 7 Hz), 3.62 (2H, q, J = 7 Hz), 3.78 (3H, s), 4.95 (2H, br.s), 6.96 (1H, br.s), 7.26 (1H, d, J = 2 Hz), 7.59 (1H, d, J = 2 Hz).

Example 3 standard preparation

(1) To a mixture of 10.0 g of 6.8-dibromo-2H-3,1-benzoxazine-2,4-1H-dione and 90 ml of tetrahydrofuran was added 1.58 g of methylhydrazine under ice-cooling, followed by stirring at room temperature within 4 hours. Water was poured into the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 4.64 g of N- (2-amino-3,5-dibromobenzoyl) -N-methylhydrazine and 0.75 g of N- (2-amino-3,5-dibromobenzoyl) -N '-methylhydrazine.

N- (2-amino-3,5-dibromobenzoyl) -N-methylhydrazine

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.25 (3H, s), 4.55 (2H, br s), 4.89 (2H, br s), 7 23 (1H, s), 7.59 (1H, s).

N- (2-amino-3,5-dibromobenzoyl) -N'-methylhydrazine

¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.51 (3H, s), 5.11 (1H, br s), 6.54 (2H, s), 7 63 (1H, d, J = 2 Hz), 7.73 (1H, d, J = 2 Hz), 10.06 (1H, br.s).

(2) To a mixture of 3.40 g of N- (2-amino-3,5-dibromobenzoyl) -N-methylhydrazine and 30 ml of tetrahydrofuran, 2.2 g of triethylamine and 2.0 g of methyl chloroformate were successively added, then stirred at room temperature. Water was poured into the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 1.10 g of compound (1-4).

Compound (1-4)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.28 (3H, s), 3.76 (3H, s), 4.96 (2H, br s), 7.00 (1H, br.s), 7.27 (1H, d, J = 2 Hz), 7.59 (1H, d, J = 2 Hz).

Example 4 standard preparation

(1) A mixture of 10.7 g of 3-bromo-1H-pyrazole, 11.8 2,3-dichloropyridine, 57.3 g of cesium carbonate and 80 ml of N, N-dimethylformamide was stirred at 100 ° C. for 8 hours. After the reaction mixture was cooled to room temperature, water was poured into the reaction mixture. The reaction mixture was extracted twice with methyl tert-butyl ether. The organic layers were combined, washed successively with water and a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 12.9 g of 2- (3-bromo-1H-pyrazol-1-yl) -3-chloropyridine.

2- (3-Bromo-1H-pyrazol-1-yl) -3-chloropyridine

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 6.51 (1H, d, J = 2 Hz), 7.31 (1H, dd, J = 8 Hz, 4 Hz), 7 91 (1H, dd, J = 8 Hz, 1 Hz), 8.04 (1H, d, J = 2 Hz), 8.45 (1H, dd, J = 4 Hz, 1 Hz).

(2) To a mixture of 5.0 g of 2- (3-bromo-1H-pyrazol-1-yl) -3-chloropyridine and 30 ml of tetrahydrofuran, 11.7 ml of a 2.0 M solution of diisopropylamide was added dropwise at -78 ° C. lithium in a mixture of heptane / tetrahydrofuran / ethylbenzene. A mixture of 3 g of ethyl formate and 10 ml of tetrahydrofuran was added dropwise at −78 ° C. to the reaction mixture, followed by stirring at room temperature for 2 hours. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 3.0 g of compound (2-1).

Compound (2-1)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.11 (1H, s), 7.47 (1H, dd, J = 8 Hz, 5 Hz), 7.96 (1H, dd, J = 8 Hz, 1 Hz), 8.52 (1H, dd, J = 5 Hz, 1 Hz), 9.79 (1H, s).

Example 5 standard preparation

(1) To obtain 3-chloro-2- (3-trifluoromethyl-1H-pyrazol-1-yl) -pyridine instead of 3-bromo-1H-pyrazole from the standard preparation example 4 (1), 3-trifluoromethyl-1H-pyrazole was used .

3-Chloro-2- (3-trifluoromethyl-1H-pyrazol-1-yl) pyridine

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 6.75 (1H, d, J = 2 Hz), 7.37 (1H, dd, J = 8 Hz, 4 Hz), 7 95 (1H, dd, J = 8 Hz, 1 Hz), 8.14 (1H, d, J = 1 Hz), 8.49 (1H, dd, J = 4 Hz, 1 Hz).

(2) To obtain compound (2-2), instead of 2- (3-bromo-1H-pyrazol-1-yl) -3-chloropyridine from the standard preparation 4 (2), 3-chloro-2- (3-trifluoromethyl) was used -1H-pyrazol-1-yl) pyridine.

[Chemical formula 22]

Compound (2-2)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.36 (1H, s), 7.51 (1H, dd, J = 8 Hz, 5 Hz), 7.99 (1H, dd, J = 8 Hz, 2 Hz), 8.54 (1H, dd, J = 5 Hz, 2 Hz), 9.86 (1H, s).

Example 6 standard preparation

(1) To obtain 2- (3-chloro-1H-pyrazol-1-yl) -3-chloropyridine, 3-chloro-1H-pyrazole was used instead of 3-bromo-1H-pyrazole from Production Example 4 (1).

2- (3-Chloro-1H-pyrazol-1-yl) -3-chloropyridine

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 6.43 (1H, d, J = 3 Hz), 7.30 (1H, dd, J = 8 Hz, 5 Hz), 7 91 (1H, dd, J = 8 Hz, 2 Hz), 8.09 (1H, d, J = 2 Hz), 8.44 (1H, dd, J = 5 Hz, 1 Hz).

(2) To obtain compound (2-3), instead of 2- (3-bromo-1H-pyrazol-1-yl) -3-chloropyridine from standard production example 4 (2), 2- (3-chloro-1H-pyrazole was used -1-yl) -3-chloropyridine.

Compound (2-3)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.02 (1H, s), 7.47 (1H, dd, J = 8 Hz, 5 Hz), 7.97 (1H, dd, J = 8 Hz, 2 Hz), 8.51 (1H, dd, J = 5 Hz, 2 Hz), 9.79 (1H, s).

Example 7 standard preparation

(1) To a mixture of 10 g of methyl carbazate and 60 ml of toluene was added dropwise a mixture of 5.86 g of acetaldehyde and 20 ml of toluene at 50 ° C, after which it was stirred for 1 hour. The reaction mixture was ice-cooled and the precipitate was filtered off. The precipitate was dried, yielding 12.1 g of methyl N'-ethylidenehydrazine carboxylate.

Methyl N'-Ethylidenehydrazine Carboxylate

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.99 (3H, d, J = 5 Hz), 3.82 (3H, s), 7.24 (1H, q, J = 5 Hz), 8.31 (1H, br s).

(2) To a mixture of 5.0 g of methyl N'-ethylidenehydrazine carboxylate and 50 ml of tetrahydrofuran, 1.95 g of sodium borohydride and 4.2 ml of methanol were successively added at 50 ° C., followed by stirring at 50 ° C. for 3 hours. After adding 50 ml of methanol at 50 ° C, the reaction mixture was stirred and heated at the boil under reflux for 3 hours. The reaction mixture was concentrated under reduced pressure and 20 ml of chloroform was added, then it was stirred at 50 ° C for 10 minutes and then filtered through celite. The resulting filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 3.70 g of methyl N'-ethylhydrazine carboxylate.

Methyl N'-ethylhydrazinecarboxylate

¹ H-NMR (DMSO-D ₆ , TMS) δ (ppm): 0.93 (3H, t, J = 7 Hz), 2.66-2.73 (2H, m), 3.54 (3H, s), 4.38-4.43 (1H, m), 8.45 (1H, s).

(3) To a mixture of 0.50 g of methyl N'-ethylhydrazinecarboxylate and 4 ml of tetrahydrofuran was added 1.36 g of 6.8-dibromo-2H-3,1-benzoxazine-2,4-1-1H-dione at room temperature and stirred and heated at the boil under reflux this mixture for 4 hours. The reaction mixture was cooled to room temperature. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.89 g of compound (1-2).

Example 8 standard preparation

(1) A mixture of 1.16 g of 4-methoxycrotonic acid (the compound described in Journal of Organic Chemistry, 1981, 46, 940-948) and 10 ml of diethyl ether was cooled with ice and gaseous hydrogen chloride was passed into it. After the mixture was saturated with gaseous hydrogen chloride, it was left to stand at room temperature overnight. A sample taken from the reaction mixture was subjected to NMR analysis and the preparation of 3-chloro-4-methoxybutyric acid was confirmed. The entire volume of the resulting reaction mixture was used as it is in the next step.

3-chloro-4-methoxybutyric acid

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 2.76 (1H, dd, J = 17 Hz, 9 Hz), 3.00 (1H, dd, J = 17 Hz, 5 Hz ), 3.42 (3H, s), 3.56 (1H, dd, J = 10 Hz, 7 Hz), 3.65 (1H, dd, J = 10 Hz, 5 Hz), 4.36-4 42 (1H, m).

(2) To the reaction mixture obtained in the above (1), 2.54 g of oxalyl dichloride was added dropwise under ice cooling. A drop of N, N-dimethylformamide was added to the reaction mixture, followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 1.45 g of 3-chloro-4-methoxybutyryl chloride.

3-chloro-4-methoxybutyryl chloride

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.26 (1H, dd, J = 18 Hz, 9 Hz), 3.41 (3H, s), 3.49-3, 54 (2H, m), 3.66 (1H, dd, J = 10 Hz, 5 Hz), 4.35-4.41 (1H, m).

(3) To a mixture of 1.45 g of 3-chloro-4-methoxybutyryl chloride and 5 ml was added dropwise to 1.29 g of 3-chloro-2-hydrazine pyridine, 1.07 g of pyridine and 10 ml of N, N-dimethylformamide. toluene, after which it was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed successively with water and a saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure to obtain 1.86 g of compound (22-1).

Compound (22-1):

[Chemical formula 23]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 2.73 (1H, dd, J = 15, 8 Hz), 2.93 (1H, dd, J = 15 Hz, 5 Hz) , 3.43 (3H, s), 3.63 (1H, dd, J = 10 Hz, 6 Hz), 3.71 (1H, dd, J = 10 Hz, 5 Hz), 4.47-4, 54 (1H, m), 6.78 (1H, dd, J = 8 Hz, 5 Hz), 7.35 (1H, br.s), 7.56 (1H, dd, J = 8 Hz, 1 Hz ), 8.07 (1H, dd, J = 5 Hz, 1 Hz), 8.66 (1H, br.s).

(4) A mixed solution of 4.5 g of sodium bicarbonate and 300 ml of N, N-dimethylformamide was heated to 130 ° C. A mixed solution of 7.48 g of compound (22-1) and 100 ml of N, N-dimethylformamide was added dropwise to it over 1 hour. The mixture was stirred at 130 ° C for 1 hour. After cooling, water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed successively with water and a saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The precipitated crystals were washed with a small amount of ethyl acetate, to obtain 2.02 g of compound (25-1).

Compound (25-1):

[Chemical formula 24]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 2.46 (1H, dd, J = 17 Hz, 1 Hz), 2.77 (1H, dd, J = 17 Hz, 8 Hz ), 3.41 (3H, s), 3.63 (1H, dd, J = 10 Hz, 8 Hz), 3.82 (1H, dd, J = 10 Hz, 5 Hz), 4.59-4 , 67 (1H, m), 7.02 (1H, dd, J = 8 Hz, 5 Hz), 7.60 (1H, s), 7.68 (1H, dd, J = 8 Hz, 2 Hz) 8.20 (1H, dd, J = 5 Hz, 2 Hz).

(5) To a mixed solution of 4.2 g of compound (25-1), 20 ml of acetonitrile and a drop of N, N-dimethylformamide was added 6 g of phosphorus bromide at room temperature, after which it was heated under reflux for 1 hour. After cooling, the reaction mixture was poured into ice water, then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 2.2 g of compound (26-1).

Compound (26-1):

[Chemical formula 25]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.23 (2H, dd, J = 10 Hz, 3 Hz), 3.34 (3H, s), 3.48 (1H, dd, J = 10 Hz, 6 Hz), 3.66 (1H, dd, J = 10 Hz, 4 Hz), 5.01-5.13 (1H, m), 6.91 (1H, dd, J = 8 Hz, 5 Hz), 7.66 (1H, dd, J = 8 Hz, 2 Hz), 8.17 (1H, dd, J = 5 Hz, 2 Hz).

(6) A mixed solution of 0.10 g of compound (26-1), 3 ml of acetonitrile, copper sulfate (catalytic amount) and drops of concentrated sulfuric acid were heated to 80 ° C. A mixed solution of 0.14 g of potassium persulfate and 4 ml of water was added dropwise to it over 2 hours, after which it was stirred at 80 ° C for 10 minutes. After cooling, water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.06 g of compound (17-1).

Compound (17-1):

[Chemical formula 26]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.23 (3H, s), 4.50 (2H, s), 6.47 (1H, s), 7.39 (1H , dd, J = 8 Hz, 5 Hz), 7.93 (1H, dd, J = 8 Hz, 2 Hz), 8.47 (1H, dd, J = 5 Hz, 2 Hz).

(7) A mixture of 0.30 g of compound (17-1), 0.49 g of potassium persulfate, 1 ml of acetonitrile and 1 ml of water was stirred at 90 ° C. for 12 hours. After cooling, water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.16 g of compound (2-1).

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.11 (1H, s), 7.47 (1H, dd, J = 8 Hz, 5 Hz), 7.96 (1H, dd, J = 8 Hz, 1 Hz), 8.52 (1H, dd, J = 5 Hz, 1 Hz), 9.79 (1H, s).

Example 9 standard preparation

(1) Under ice cooling, 4 g of 4-methoxycrotonic acid and a drop of N, N-dimethylformamide were mixed and 16.5 g of oxalyl chloride was added dropwise, after which it was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product. The entire amount of this crude product was used in the next step as it is.

4-methoxycrotonoyl chloride:

[Chemical formula 27]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.43 (3H, s), 4.18 (2H, dd, J = 4 Hz, 2 Hz), 6.34 (1H, dt, J = 15 Hz, 2 Hz), 7.19 (1H, dt, J = 15 Hz, 4 Hz).

(2) The crude product obtained in the above (1), 50 ml of N, N-dimethylformamide and 10 g of pyridine was stirred at room temperature. 4.5 g of 3-chloro-2-hydrazine pyridine was added thereto. The mixture was stirred for 1 hour, and then left to stand overnight at room temperature. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with a saturated solution of ammonium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The precipitated crude crystals were washed with a small amount of ethyl acetate, to obtain 2.3 g of compound (24-1).

Compound (24-1):

[Chemical formula 28]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.41 (3H, s), 4.10-4.15 (2H, m), 6.21 (1H, dt, J = 15 Hz, 2 Hz), 6.76 (1H, dd, J = 8 Hz, 5 Hz), 6.98 (1H, dt, J = 15 Hz, 4 Hz), 7.48-7.60 (2H , m), 8.07 (1H, dd, J = 5 Hz, 1 Hz), 8.45 (1H, br.s).

(3) A mixture of 8.0 g of compound (24-1) and 24.0 g of acetonitrile was cooled in a water bath and gaseous hydrogen chloride was passed under stirring. After stirring while passing hydrogen chloride gas for about 3 hours, the reaction mixture was concentrated under reduced pressure. A saturated sodium bicarbonate solution was poured into the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure to obtain 8.97 g of compound (22-1).

Example 10 standard preparation

(1) To a mixture of 0.48 g of compound (25-1) and 10 ml of acetonitrile, 0.25 g of methanesulfonyl chloride and 0.30 g of triethylamine were successively added under ice-cooling, after which they were stirred at 0 ° C for 1 hour. Water was poured into the reaction mixture, then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.32 g of compound (27-1).

Compound (N-1):

[Chemical formula 29]

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.14 (2H, d, J = 10 Hz), 3.36 (3H, s), 3.47 (3H, s), 3.55 (1H, dd, J = 10 Hz, 6 Hz), 3.66-3.74 (1H, m), 5.10-5.21 (1H, m), 6.87 (1H, dd , J = 8 Hz, 5 Hz), 7.64 (1H, dt, J = 8 Hz, 1 Hz), 8.14 (1H, dt, J = 5 Hz, 1 Hz).

(2) A mixture of 0.53 g of compound (27-1) and 1.2 g of a 33 wt.% Solution of hydrogen bromide-acetic acid was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water, and then extracted with ethyl acetate. The organic layer was washed with a saturated sodium hydrogen carbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.30 g of compound (26-1).

The following are specific examples of compound (1).

[Chemical formula 30]

Table 3 Connection number R ¹ R ² R ³ R ⁴ R ⁵ 1-1 CH ₃ CH ₃ CH ₃ Br Br 1-2 CH ₃ CH ₂ H CH ₃ Br Br 1-3 CH ₃ H CH ₃ CH ₃ Cl 1-4 CH ₃ H CH ₃ Br Br 1-5 (CH ₃ ) ₂ CH H CH ₃ Br Br 1-6 CH ₃ CH ₃ CH ₃ CH ₃ Cl 1-7 CH ₃ H CH ₃ CH ₃ CN 1-8 CH ₃ CH ₃ CH ₃ CH ₃ CN 1-9 CH ₃ H CH ₃ Cl Cl 1-10 CH ₃ H CH ₃ CH ₂ Cl Cl 1-11 CH ₃ CH ₃ CH ₃ Cl Cl 1-12 CH ₃ CH ₃ CH ₃ Br Cl 1-13 CH ₃ CH ₂ H CH ₃ Cl Cl 1-14 CH ₃ (CH ₂ ) ₂ H CH ₃ Br Br 1-15 CH ₃ CH ₃ CH ₂ CH ₃ Br Br 1-16 CH ₃ CH ₂ CH ₃ CH ₃ Br Br 1-17 CH ₃ CH ₂ CH ₃ CH ₂ CH ₃ Br Br 1-18 CH ₃ CH ₂ H CH ₃ CH ₃ Cl 1-19 CH ₃ CH ₂ H CH ₃ CH ₃ CN

The physical properties of some of the compounds (1) are given.

Compound (1-1)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.11-3.18 (6H, m), 3.76 (3H, br s), 4.86 (1.4H, br. s), 5.23 (0.6H, br.s), 7.17-7.25 (1H, m), 7.57 (1H, d, J = 2 Hz).

Compound (1-2)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.21 (3H, t, J = 7 Hz), 3.62 (2H, q, J = 7 Hz), 3.78 (3H, s), 4.95 (2H, br.s), 6.96 (1H, br.s), 7.26 (1H, d, J = 2 Hz), 7.59 (1H, d, J = 2 Hz).

Compound (1-4)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.28 (3H, s), 3.76 (3H, s), 4.96 (2H, br s), 7.00 (1H, br.s), 7.27 (1H, d, J = 2 Hz), 7.59 (1H, d, J = 2 Hz).

Compound (1-15)

¹ H-NMR (DMSO-d ₆ , 100 ° C, TMS) δ (ppm): 1.09 (3H, t, J = 7 Hz), 3.12 (3H, s), 3.40 -3.52 (2H, m), 3.70 (3H, s), 5.23 (2H, br.s), 7.20 (1H, d, J = 2 Hz), 7.62 (1H, d, J = 2 Hz).

Compound (1-16)

¹ H-NMR (DMSO-d ₆ , 100 ° C, TMS) δ (ppm): 1.15 (3H, t, J = 7 Hz), 3.07 (3H, s), 3.45 -3.60 (2H, m), 3.67 (3H, s), 5.19 (2H, br.s), 7.20 (1H, d, J = 2 Hz), 7.61 (1H, d, J = 2 Hz).

Compound (1-17)

¹ H-NMR (DMSO-d ₆ , 100 ° C, TMS) δ (ppm): 1.09-1.17 (6H, m), 3.40-3.55 (4H, m), 3.69 (3H, s), 5.19 (2H, br.s), 7.22 (1H, d, J = 2 Hz), 7.62 (1H, d, J = 2 Hz).

The following are specific examples of compound (2).

[Chemical formula 31]

Table 4 Connection number R ⁶ R ⁷ 2-1 Br Cl 2-2 CF ₃ Cl 2-3 Cl Cl

The physical properties of some compounds are given (2).

Compound (2-1)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.11 (1H, s), 7.47 (1H, dd, J = 8 Hz, 5 Hz), 7.96 (1H, dd, J = 8 Hz, 1 Hz), 8.52 (1H, dd, J = 5 Hz, 1 Hz), 9.79 (1H, s).

Compound (2-2)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.36 (1H, s), 7.51 (1H, dd, J = 8 Hz, 5 Hz), 7.99 (1H, dd, J = 8 Hz, 2 Hz), 8.54 (1H, dd, J = 5 Hz, 2 Hz), 9.86 (1H, s).

Compound (2-3)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.02 (1H, s), 7.47 (1H, dd, J = 8 Hz, 5 Hz), 7.97 (1H, dd, J = 8 Hz, 2 Hz), 8.51 (1H, dd, J = 5 Hz, 2 Hz), 9.79 (1H, s).

The following are specific examples of compound (17).

[Chemical formula 32]

Table 5 Connection number R ^c R ⁶ R ⁷ 17-1 CH ₃ Br Cl 17-2 CH ₃ Cl Cl

The physical properties of some compounds are given (17).

Compound (17-1)

¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 3.23 (3H, s), 4.50 (2H, s), 6.47 (1H, s), 7.39 (1H , dd, J = 8 Hz, 5 Hz), 7.93 (1H, dd, J = 8 Hz, 2 Hz), 8.47 (1H, dd, J = 5 Hz, 2 Hz).

Further, as an example of a standard composition, examples of a composition based on the compound (3) used as an agent for controlling harmful arthropods will be described. The term "part (s)" means the mass part (s).

Standard composition example 1

A mixture of 10 parts of any of the compounds (3-1) to (3-43), 35 parts of white coal containing 50 parts of ammonium salt of polyoxyethylene alkyl ether sulfate, and 55 parts of water are finely ground by wet grinding to obtain a 10% flowable composition.

The following standard test examples show that compound (3) is applicable as an active ingredient in an anti-arthropod control agent.

Standard Test Case 1

The compositions of the compounds from (3-1) to (3-23), from (3-25) to (3-27), from (3-29) to (3-31) and (3-33), obtained in the example standard composition was diluted with water, so that the concentration of the active ingredient was 50 ppm, to obtain test solutions for spraying.

Simultaneously, cabbage was planted in a plastic cup and grown until a third true leaf or fourth true leaf appeared. A spray solution of 20 ml / glass was sprayed onto the cabbage. After the solution was dried on cabbage, 10 larvae of the cabbage moth (Plutella xylostella) of the third age stage were placed on the cabbage. After 5 days, cabbage moth was counted and the control value was calculated according to the following equation:

Reference value (%) = {1- (Cb × Tai) / (Cai × Tb)} × 100,

where Cb: number of tracks in the untreated area before processing

Cai: number of tracks in the untreated area when observed

Tb: the number of tracks in the treated area before processing

Tai: number of tracks in the treated area when observed

As a result, each of the test solutions for spraying based on compounds from (3-1) to (3-23), from (3-25) to (3-27), from (3-29) to (3-31) and (3-33) showed a control value of 80% or more.

Standard Test Example 2

The compositions of the compounds from (3-1) to (3-23), from (3-25) to (3-27), from (3-29) to (3-31) and (3-33), obtained in the example standard composition was diluted with water, so that the concentration of the active ingredient was 500 ppm, to obtain test solutions for spraying.

At the same time, cucumbers were planted in a plastic cup and grown until the first true leaf appeared. About 30 cotton aphid larvae (Aphis gossypii) were placed on cucumbers. After a day, a spray solution of 20 ml / glass was sprayed onto the cucumbers. Six days after spraying, cotton aphids were counted and a control value was calculated using the following equation:

Reference value (%) = {1- (Cb × Tai) / (Cai × Tb)} × 100,

where Cb: number of insects in the untreated area before treatment

Cai: number of insects in the untreated area when observed

Tb: number of insects in the treated area before treatment

Tai: number of insects in the treated area when observed

As a result, each of the test solutions for spraying based on compounds from (3-1) to (3-23), from (3-25) to (3-27), from (3-29) to (3-31), and (3-33) showed a control value of 90% or more.

Industrial applicability

In accordance with the method of the present invention, it is possible to obtain a new compound (3) having excellent regulatory activity against harmful arthropods.

Claims (3)

1. The method of obtaining the amide compound represented by the formula (3):

where R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ^{7 are} defined below, including the introduction into the interaction of aniline compounds represented by formula (I):

where R ¹ represents a C1-C6 alkyl group optionally substituted by at least one halogen atom,
R ² represents a hydrogen atom or a C1-C6 alkyl group optionally substituted with at least one halogen atom,
R ³ represents a C1-C6 alkyl group optionally substituted by at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted by at least one halogen atom, a C3-C6 alkenyl group optionally substituted by at least , one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom,
R ⁴ represents a halogen atom or a C1-C6 alkyl group optionally substituted with at least one halogen atom, and
R ⁵ represents a hydrogen atom, a halogen atom, a cyano group or a C1-C6 alkyl group optionally substituted with at least one halogen atom, with an aldehyde compound represented by the formula (2):

where R ⁶ represents a hydrogen atom, a halogen atom, a cyano group, a C1-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted by at least one halogen atom, a C1-C6 alkylsulfinyl group, optionally substituted by at least one halogen atom, or a C1-C6 alkylsulfonyl group optionally substituted by at least one halogen atom, and
R ⁷ represents a halogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, in
a solvent in the presence of an oxidizing agent selected from the following group A: (a) oxygen, (b) peroxide, and (c) chromic acid or a salt thereof. 2. The method according to claim 1, in which the oxidizing agent is (a) oxygen or (b) peroxide. 3. The method of claim 1, wherein (b) the peroxide is carboxylic acid peroxide.